Skin damage represents a major public health problem. For example, endstage skin damage in the form of non-melanoma skin cancers are the most frequently diagnosed malignancies in the USA. The occurrence of DNA damage and cellular responses to DNA damage are major factors in skin pathologies, including skin cancer. A compelling body of evidence now indicates that there are therapeutic candidates for skin damage prevention. However, a major challenge for the development of prevention strategies for skin damage relates to the difficulty of delivering micronutrients to skin. In research completed under Phase I, it was demonstrated that topical delivery of micronutrients to skin cells is feasible and that such delivery provides prevention benefit. This is a Phase II SBIR application to develop technology for delivering specific micronutrients to skin cells to prevent skin damage and potentially skin cancer. The proposed research will test the hypotheses that a strategy employing micronutrients to limit skin damage by multiple mechanisms for preventing DNA damage, enhancing DNA repair, preventing immune suppression, and preventing migration of transformed cells from epidermis to dermis will limit skin damage including skin cancer and that topical delivery of key micronutrients to skin cells represents the most efficacious approach for prevention of skin damage and that delivery can be achieved by the development of pronutrients specifically tailored for targeted delivery to skin. The specific aims of this proposal are to design, synthesize, characterize and evaluate the topical delivery properties of specific pronutrients (niacin, vitamin E, folate, Q1O, and lipoate) to evaluate the safety, tolerance, and efficacy, singly and in combinations of pronutrients having optimal delivery properties in a mouse model. The efficacy of delivery of the lead candidate for each pronutrient determined in the mouse model will be evaluated in the porcine model, the most predictive animal model of human skin. The successful completion of these objectives will complete early phase commercial development of technology intended to translate to a product that will allow optimization of skin health and prevent skin damage, including skin cancer.